The present invention relates to a novel process for preparing aromatic amines using palladaphosphacyclobutanes.
Aromatic amines, in particular substituted anilines, are of great industrial importance as precursors for dyes, fine chemicals, agrochemicals and intermediates for active compounds.
The preparation of substituted anilines is generally carried out industrially by nitration of a corresponding aromatic and subsequent hydrogenation. Since nitrations take place under drastic reaction conditions, many anilines having a complex substitution pattern can be prepared only with difficulty, if at all, by this route.
Palladium-catalyzed aminations of iodoaromatics, bromoaromatics and chloroaromatics leading to substituted anilines are described in A. S. Guram et al., Angew. Chem. 1995, 107, 1459. These reactions are carried out under comparatively mild reaction conditions and can therefore also be used for the synthesis of anilines having a complex substitution pattern. The iodoaromatics and bromoaromatics used as starting materials are significantly more expensive and less readily available than the chloroaromatics.
DE-A1-196 50 213 discloses a process for the amination of chloroaromatics using trans-di-xcexc-acetatobis(o-(di-o-tolylphosphino)benzyl)dipalladium, if desired in the presence of halide cocatalysts. In general, 1 mol % of catalyst (corresponding to 2 mol % of Pd) is used.
Particularly in the case of chloroaromatics, large amounts of catalyst, in general from 1 to 5 mol %, are usually added in order to achieve industrially useful conversions. Owing to the complexity of the reaction mixture, simple recycling of the catalyst is not possible, so that the catalyst costs generally stand in the way of industrial implementation.
There is therefore a great need for a process for preparing aromatic amines which does not have the abovementioned disadvantages, is suitable for industrial implementation and gives aromatic amines in high yield and purity.
This object is surprisingly achieved by the use of particular palladaphosphacyclobutanes as catalysts.
The present invention provides a process for preparing aromatic amines of the formula (I)
Arxe2x80x94[NR6R7]nxe2x80x83xe2x80x83(I)
where
n is 1, 2 or 3,
Ar is unsubstituted or substituted phenyl, furanyl, pyrryl, pyridinyl, naphthyl or quinolinyl, where the substituents are 1, 2, 3, 4, 5 or 6, preferably 1, 2 or 3, in number and are selected from the group consisting of C1-C8-alkyl, C3-C8-cycloalkyl, C1-C8-alkoxy, C1-C8-acyloxy, C6-C10-aryloxy, C6-C10-aryl, benzyl, fluorine, chlorine, bromine, OH, NO2, OSO2CF3, CN, COOH, CHO, SO3H, SO2R, SOR, where R is C1-C4-alkyl, C6-C10-aryl or benzyl, NH2, NHxe2x80x94C1-C8-alkyl, Nxe2x80x94(C1-C8-alkyl)2, CF3, NHCOxe2x80x94C1-C4-alkyl, Nxe2x80x94C1-C4-alkyl-COxe2x80x94C1-C4-alkyl, COOxe2x80x94C1-C8-alkyl, CONH2, COxe2x80x94C1-C8-alkyl, NHCOH, NCOOxe2x80x94C1-C4-alkyl, CO-phenyl, COO-phenyl, CHCHxe2x80x94CO2xe2x80x94C1-C8alkyl, CHCHCO2H, PO-phenyl2, POxe2x80x94(C1-C4-alkyl)2, 5-membered heteroaryl and 6-membered heteroaryl in each case containing O, S and/or N as heteroatoms; and
R6 and R7 are, independently of one another, hydrogen, C1-C12-alkyl, C1-C12-hydroxyalkyl, unsubstituted or substituted phenyl, or C3-C8-cycloalkyl, or R6 and R7 together with the N atom form a 5- or 6-membered aliphatic or aromatic ring which may contain 1 or 2 further atoms selected from the group consisting of N, O and S as heteroatoms,
by reacting haloaromatics of the formula (II)
Arxe2x80x94Halxe2x80x83xe2x80x83(II)
where Hal is Cl, Br or I,
with an amine of the formula (III)
R6R7NHxe2x80x83xe2x80x83(III)
wherein the reaction is carried out in the presence of a palladaphosphacyclobutane of the formula (IV) 
where
R1a, R2a are, independently of one another, hydrogen, C1-C4-alkyl, C3-C12-cycloalkyl, C1-C4-alkoxy, fluorine, Nxe2x80x94(C1-C4-alkyl)2, CO2xe2x80x94C1-C4-alkyl, OCOxe2x80x94C1-C4-alkyl or substituted or unsubstituted aryl,
R3a, R4a, R5a and R6a are, independently of one another C1-C8-alkyl, C3-C12cycloalkyl, substituted or unsubstituted aryl;
or R1a and R2a, or R2a and R3a, or R3a and R4a together form an aliphatic ring having from 4 to 10 carbon atoms,
or R5a and R6a together with the P atom form a saturated or unsaturated 4- to 9-membered ring, or R4a and R5a form a bridging 1,xcfx89-alkanediyl chain having from 2 to 7 carbon atoms, and
Y is an anion of an inorganic or organic acid, an xcex1,xcex3-diketo compound or a 5- to 6-membered nitrogen-containing heterocycle,
in the presence of a base and in the presence or absence of an ionic halide in a solvent at temperatures of from 20 to 200xc2x0 C.
The synthesis of the palladaphosphacyclobutanes is described in DE-A1-196 47 584. Preference is given to compounds of the formula (IV) in which
R1a and R2a are, independently of one another, hydrogen, methyl, ethyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, fluorine, phenyl, tolyl or naphthyl;
R3a and R4a are, independently of one another, C1-C4-alkyl, C5-C6-cycloalkyl, substituted or unsubstituted C6-C10-aryl or R3a and R4a together form an aliphatic ring having from 5 to 6 carbon atoms;
R5a and R6a are, independently of one another, C1-C4-alkyl, C5-C6-cycloalkyl, phenyl, naphthyl, anthracenyl, each of which may be unsubstituted or substituted by from 1 to 3 CF3xe2x80x94, C1-C4-alkyl or C1-C4-alkoxy groups;
and Y is acetate, propionate, benzoate, chloride, bromide, iodide, fluoride, sulfate, hydrogensulfate, nitrate, phosphate, trifluoromethanesulfonate, tetrafluoroborate, tosylate, mesylate, acetylacetonate, hexafluoracetylacetonate or pyrazolyl.
Particular preference is given to compounds of the formula (IV) in which
R1a and R2a are, independently of one another, hydrogen or methyl;
R3a and R4a are, independently of one another, methyl, ethyl or phenyl;
R5a and R6a are, independently of one another, phenyl, naphthyl, o-trifluoromethylphenyl, o-trifluoromethyl-p-tolyl, o-trifluoromethyl-p-methoxyphenyl, o-methoxyphenyl, o,p-dimethoxyphenyl, o,o,p-trimethoxyphenyl, anthracenyl, tert-butyl, n-butyl, isopropyl, isobutyl, cyclohexyl or 1-methylcyclohexyl.
Very particular preference is given to the following compounds of the formula (IV):
trans-di-xcexc-acetatobis[2-[bis(1,1-dimethylethyl)phosphino]-2-methylpropyl-C,P]dipalladium(II),
trans-di-xcexc-acetatobis[2-[1,1-dimethylethyl)phenylphosphino]-2-methylpropyl-C,P]dipalladium(II),
trans-di-xcexc-chlorobis[2-[bis(1,1-dimethylethyl)phosphino]-2-methylpropyl-C,P]dipalladium(II),
trans-di-xcexc-chlorobis[2-[(1,1-dimethylethyl)phenylphosphino]-2-methylpropyl-C,P]dipalladium(II),
trans-di-xcexc-bromobis[2-[bis(1,1-dimethylethyl)phosphino]-2-methylpropyl-C,P]dipalladium(II) and
trans-di-xcexc-bromobis[2-[(1,1-dimethylethyl)phenylphosphino]-2-methylpropyl-C,P]dipalladium(II).
The palladium catalysts are synthesized before the actual reaction, but can also be generated in situ, as described, for example, in EP-A1-0802173. However, in the case of a prolonged reaction time, the in-situ mixtures (molar ratio Pd:P=1:1) prove to have little stability and frequently lead to deposition of palladium. This disadvantage is surprisingly overcome by the use according to the invention of previously prepared palladaphosphacyclobutanes.
Palladaphosphacyclobutanes generally have a dimeric structure. However, in the case of particular compounds (e.g. Y=acetylacetone, hexafluoracetylacetone) monomeric, oligomeric or even polymeric structures may be present.
During the catalysis cycle, the dimeric structure is broken up by bridge cleavage reactions with inorganic and organic nucleophiles, so that the mononuclear complexes of the formulae (V) and (VI) 
may be the actual catalytically active species. The complexes of the formulae (V) and (VI) are in equilibrium with the dimers used and are uncharged or anionic. The mononuclear complex of the formula (V) may have further donor ligands on the palladium atom.
The palladaphosphacyclobutanes used have very high activity and surprisingly high stability.
The stability of the palladaphosphacyclobutanes in solution can be increased further by addition of alkali metal salts, alkaline earth metal salts and transition metal salts of transition groups VI to VII. The addition of ionic halides and pseudohalides (e.g. CNxe2x88x92) in particular results in significant yield increases and improvements in the life of the homogeneous catalyst in the reaction of chloroaromatics.
The ionic halide is preferably an alkali metal, ammonium, alkylammonium, alkylolammonium or phosphonium halide, in particular an alkali metal or ammonium halide, where halide is chloride, bromide or iodide, in particular bromide or chloride. Examples are ammonium bromide, lithium bromide, sodium bromide, potassium bromide, tetrabutylphosphonium bromide, ammonium chloride, dimethylammonium chloride, diethanolammonium chloride, lithium chloride, sodium chloride, potassium chloride, tetrabutylphosphonium chloride, ammonium iodide, lithium iodide, sodium iodide, potassium iodide and/or tetrabutylphosphonium iodide, in particular lithium chloride, ammonium chloride, dimethylammonium chloride, and/or diethanolammonium chloride.
The ionic halide is preferably used in an amount of from 0.1 to 100 mol %, in particular from 3 to 50 mol %, based on the haloaromatic used. In the form of a liquid salt, it can also serve as solvent.
Owing to the activity and stability of the catalyst, it is possible to use very small amounts of catalyst, so that the catalyst costs are no longer cost-limiting for the corresponding process, in contrast to conventional processes.
The catalyst can be used in amounts of from 0.001 to 5 mol %, preferably from 0.005 to 2 mol %, in particular from 0.01 to 0.9 mol %, based on the haloaromatic of the formula (II).
Preferred haloaromatics of the formula (II) are those of the formulae (II a), (II b), (II c) and (II d) 
where
Hal is as defined above
R1 to R5 are identical or different and are each hydrogen, C1-C4-alkyl, C5-C6-cycloalkyl, C1-C4-alkoxy, C1-C6-acyloxy, phenoxy, phenyl, fluorine, chlorine, OH, NO2, CN, COOH, NHxe2x80x94C1-C4-alkyl, N(C1-C4-alkyl)2, NH2, COOxe2x80x94C1-C4-alkyl, COxe2x80x94C1-C4-alkyl, CF3, SO3H, SO2R, where R is methyl, ethyl or phenyl.
The radical Hal can be located at any position on the aromatic ring.
Preferred amines of the formula (III) are ones in which
R6 and R7 are identical or different and are each hydrogen, C1-C6-alkyl, C1-C6-hydroxyalkyl, phenyl or C5-C6-cycloalkyl, or R6 and R7 together with the N atom form a piperazine, piperidine, morpholine, imidazole, pyrazole or pyrrolidine ring.
The process of the invention makes it possible to prepare, for example, compounds such as arylpiperazines, arylpiperidines, aryldibutylamines, arylmorpholines, arylphenylmethylamines, aryldiethylamines and aryldiphenylamines, where aryl is preferably phenyl, methoxyphenyl, trifluoromethylphenyl, acetylphenyl, fluorophenyl, difluorophenyl, chlorophenyl, methylphenyl, pyridyl or naphthyl, in a simple manner.
The amine of the formula (III) is advantageously used in an amount of from 1 to 1.3 mol, preferably from 1 to 1.1 mol, per mol of haloaromatic of the formula (II) and per Hal atom to be replaced.
Solvents employed are generally inert organic solvents. Well suited solvents are aromatic hydrocarbons such as toluene, xylenes, anisole, tetralin, and aliphatic ethers such as tetrahydrofuran, dimethoxyethane, ethylene glycol dimethyl ether, dioxane, tetrahydropyran and formaldehyde acetals. The reaction proceeds at temperatures of from 20 to 200xc2x0 C., preferably at temperatures from 80 to 180xc2x0 C., in particular from 100 to 150xc2x0 C.
In the process of the invention, the amines are preferably reacted with haloaromatics in the presence of a strong base whose pKa is preferably  greater than 10. Bases which can be employed are, for example, alkali metal alkoxides or alkaline earth metal alkoxides, alkali metal amides or alkaline earth metal amides and also butyllithium or phenyllithium. Particularly preferred bases are alkali metal and alkaline earth metal alkoxides such as sodium tert-butoxide, potassium tert-butoxide, lithium tertbutoxide, sodium phenoxide or potassium phenoxide, potassium carbonate, sodium hexamethyldisilazide and lithium hexamethyldisilazide. Very particular preference is given to sodium tert-butoxide, potassium tert-butoxide and lithium tert-butoxide.
The base is preferably used in an amount of from 0.5 to 5 equivalents, in particular from 0.8 to 3 equivalents and very particularly preferably from 1 to 2 equivalents, based on the haloaromatic used.